Ulcerative colitis is known as one of intractable inflammatory diseases, and it was reported that the number of the patients (recipient for specified disease) was 77,073 in 2002 being increasing by 5,000 every year. The ulcerative colitis is an inflammatory disease of the colon where the erosion or ulcer is formed in the mucous membrane of the large intestine. It is considered that this disease is caused by involvement in enteric bacteria, abnormal autoimmune reaction wherein the immune functions do not work normally, or involvement in dietary change, however, they have not been clarified yet. The characteristic symptoms may be diarrhea with or without melena and frequent abdominal pain. The lesion has the property of extending continuously to the ascending (orifice side) from the rectum, further to the entire colon from the rectum in maximum. This disease is classified by extension of the lesion, the progress, etc. as described below:
(1) classification by extension of the lesion: total colitis, left side colitis and rectitis;
(2) classification of the stage: active phase and remission phase;
(3) classification by the severity: mild, moderate, severe and fulminant; and
(4) classification by the clinical progress: exacerbation remission, chronic persistent, acute fulminant and initial paroxysmal types.
For diagnosis of the ulcerative colitis, persistent or repetitive mucous blood, bloody stool, or past histories thereof are used. In addition, endoscopy in the colon or sigmoid colon are combined with biopsy, and if necessary, X-ray inspection of enema and endoscopy in the whole large intestine which require high technology and excessive cost are performed. Selection of the optimum therapy including whether the operation is required or not, selection of therapeutic drugs, determination for discontinuation of the therapeutic drug's administration is firstly conducted based on analysis of data obtained from the clinical symptoms. Further, the endoscopy is conducted to confirm the pathologic. However, the method was accompanied by risk of bleeding due to perforation and damage of intestinal mucosa, if the ulcerative colitis is in the active phase, and also the frequent examinations have been accompanied by burden and suffering for patients examined, in addition to excessive charge on the medical economy.
Also, prostaglandins (hereinafter referred to as PGs) and their derivatives have been reported to have relationship with various pathologies in vivo, and methods for quantifying trace PGs in a simple operation have been known. These measurements include gas chromatography-mass spectrometry (GC-MS), radioimmunoassay (RIA), enzyme immunoassay (EIA), etc. Prostaglandin E2 (PGE) is known as an important chemical mediator involved in inflammatory reactions in vivo, and the method wherein PGE Main Urinary Metabolites (hereinafter referred to as “PGE-MUM”) in urine are measured by the enzyme immunoassay has been reported (Japanese Patent Laid-Open No. 61-11664).
In addition, there has been an attempt by the present inventors at relating values obtained by measuring the PGE-MUM from the urine sample obtained from patients with ulcerative colitis to total scores (revised Talstad scores) of digitized scores of plural clinical symptoms (clinical disease activity) of patients with ulcerative colitis (Digestion 2000; 61: 201-206).
On the other hand, an interstitial pneumonitis is known as one of intractable inflammatory diseases.
The interstitial pneumonitis is a general name of cases which finally causes fibrosing of pulmonary alveolus accompanying inflammation of the stromata, including idiopathic pulmonary fibrosis, non-specific interstitial pneumonitis, idiopathic organizing pneumonia being known.
For the interstitial pneumonitis, the onset mechanism has not been fully elucidated, therefore, high experience is required for the diagnosis, and accompanied by difficulty that total judgement for cases of patients for individual cases, examination results of various collected data, etc.
To resolve these problems, investigation is made for relating the measured values of amounts of osteopontin in plasma to the symptoms of the interstitial pneumonitis (Japanese Patent Laid-Open No. 2005-030852).
Also as markers for determining symptoms of the interstitial pneumonitis, surfactant protein D (SP-D), surfactant protein A (SP-A), antigen KL-6 of sialated suger chain and the like are known.
These markers are, however, detected as the result after the symptoms of the interstitial pneumonitis have proceeded, it has been found that the method depending on these markers is not always appropriate as measures for determining the phase of the interstitial pneumonitis stages.